Author: ["Yosuke Funato","Tatsuo Michiue","Makoto Asashima","Hiroaki Miki"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Dishevelled (Dvl) transduces signals from the Wnt receptor, Frizzled, to downstream components, leading to the stabilization of β-catenin and subsequent activation of the transcription factor T cell factor (TCF) and/or lymphoid enchancer factor (LEF)1,2,3. However, the mechanism of Dvl action remains unclear. Here, we report that nucleoredoxin (NRX)4, a thioredoxin (TRX) family protein, interacts with Dvl. Overexpression of NRX selectively suppresses the Wnt–β-catenin pathway and ablation of NRX by RNA-interference (RNAi) results in activation of TCF, accelerated cell proliferation and enhancement of oncogenicity through cooperation with mitogen-activated extracellular signal regulated kinase kinase (MEK) or Ras. We find that cells respond to H2O2 stimulation by activating TCF. Redox-dependent activation of the Wnt–β-catenin pathway occurs independently of extracellular Wnts and is impaired by RNAi of NRX . In addition, association between Dvl and NRX is inhibited by H2O2 treatment. These data suggest a relationship between the Wnt–β-catenin pathway and redox signalling through redox-sensitive association of NRX with Dvl.Cite this article
Funato, Y., Michiue, T., Asashima, M. et al. The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt–β-catenin signalling through Dishevelled. Nat Cell Biol 8, 501–508 (2006). https://doi.org/10.1038/ncb1405 